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Testicular hyaluronidase induces tubular structures of endothelial cells grown in three‐dimensional colagen gel through a CD44‐mediated mechanism
Author(s) -
Rahmanian Mehdi,
Heldin Paraskevi
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10087
Subject(s) - hyaluronidase , angiogenesis , basic fibroblast growth factor , endothelial stem cell , biology , cd44 , microbiology and biotechnology , chemistry , growth factor , biochemistry , receptor , cell , enzyme , cancer research , in vitro
Cultured brain capillary endothelial cells grown in a 3‐dimensional collagen gel can form tubular structures after stimulation by angiogenic factors. We found that treatment of such cultures with testicular hyaluronidase led to formation of tubular structures and cell survival. Anion‐exchange chromatography of the enzyme preparation on a MonoQ column revealed the presence of the angiogenic factor basic fibroblast growth factor (bFGF) in the flow‐through fraction, as determined by immunoblotting; part of the effect on endothelial cell morphogenesis could thus be ascribed to bFGF. However, adsorbed fractions eluted with increasing concentrations of NaCl, which exhibited hyaluronan‐degrading activity at neutral pH, did not contain bFGF but were still able to induce tube‐like structures of the endothelial cells. Streptomyces hyaluronidase failed to evoke the same effect. Interestingly, blocking of hyaluronan binding to CD44 receptors by the monoclonal antibody KM114 inhibited the effect of hyaluronidase, but not of bFGF, on endothelial cell tube formation. Our data suggest a CD44‐mediated specific role for certain populations of testicular hyaluronidase in the induction of angiogenesis. © 2001 Wiley‐Liss, Inc.